The influence of visual cortex on the midbrain superior colliculus (SC) is essential for normal visual orientation behaviors, and the loss of such capabilities after unilateral cortical lesions has long been presumed to reflect the loss of excitatory cortico-colliculus inputs to the ipsilateral SC. Surprisingly, however, these lesion-induced deficits in visual orientation are ameliorated by a second lesion; one that eliminates basal ganglia inputs to the SC from the opposite side of the brain. This suggests that the basal ganglia is a critical but poorly understood factor, not only in the manifestation of this particular dysfunction, but also in the normal interhemispheric control of the subcortical processes that underlie visuomotor behavior. We suggest that visual cortex lesions produce visual hemineglect in part because cortical damage induces secondary alterations bilaterally within the basal ganglia. The most important of these changes in the present context are those in the basal ganglia output signals that reach the SC from the opposite side of the brain (i.e., the crossed nigro-colliculus pathway), which ultimately renders the SC ipsilateral to the cortical lesion nonfunctional. We suggest that cortical lesions that produce this dysfunction do so by inducing NMDA-mediated processes that act within the input structures of the basal ganglia on the opposite side of the brain and become, in turn, manifested in its crossed nigro-colliculus output signals. We propose to investigate how the basal ganglia is affected by cortical lesions and to evaluate whether pretreatment with NMDA antagonists can preclude these visuomotor deficits by preventing the normal sequelae of secondary events that normally follow visual cortical lesions. The proposed investigations will involve a multidisciplinary anatomical, behavioral, pharmacological, and physiological approach. The results of these experiments will provide insight into the delicate interplay between the basal ganglia and SC that is essential for SC-mediated visuomotor processes, examine how basal ganglia-SC control is orchestrated by inputs from visual cortex, and determine the changes in basal ganglia-SC processes that are induced by visual cortical lesions that disrupt the physiology of the SC and the visuomotor behaviors it controls. Understanding the strategic role of the basal ganglia in mediating visual hemineglect after visual cortical lesions may facilitate the development of therapeutic strategies for ameliorating this debilitating condition in human patients.